Abstract
Background:
Unspecified functional bowel disorder (FBD-U) is a Rome IV diagnosis of exclusion and occurs when patients report bowel symptoms but do not meet the criteria for other functional bowel disorders (FBDs: irritable bowel syndrome (IBS), functional constipation (FC), functional diarrhea (FDr) or functional bloating). Previous research suggests that FBD-U is as/more common than IBS.
Methods:
1,501 patients at a single-center tertiary care center completed an electronic survey. Study questionnaires included Rome IV diagnostic questionnaires, anxiety, depression, sleep, healthcare utilization, and bowel symptom severity measures.
Results:
813 patients met Rome IV criteria for a FBD and 194 patients (13.1%) met criteria for FBD-U, representing the second most common FBD after IBS. Severity of abdominal pain, constipation and diarrhea were lower in FBD-U compared to other FBDs, while healthcare utilization was similar among the groups. Scores on measures of anxiety, depression, and sleep disturbances were similar in FBD-U compared to FC and FDr, but were less severe than IBS. Between 25-50% of FBD-U patients did not meet Rome IV criteria for other FBDs due to timing of onset of the target symptom (e.g., constipation for FC, diarrhea for FDr, abdominal pain for IBS).
Conclusions:
FBD-U, by Rome IV criteria, is highly prevalent in clinical settings. These patients are not represented in mechanistic studies or clinical trials for not having met Rome IV criteria for other FBDs. Making future Rome criteria less stringent would minimize the number fulfilling criteria for FBD-U and maximize the true representation of FBDs in clinical trials.
Introduction
Functional bowel disorders (FBD) are a spectrum of chronic gastrointestinal disorders characterized by abdominal pain, bloating, distention, and/or bowel habit abnormalities (eg, constipation, diarrhea, or mixed constipation and diarrhea). Per the ROME IV criteria(1), the FBDs are classified into 5 distinct categories: irritable bowel syndrome (IBS), functional constipation (FC), functional diarrhea (FDr), functional abdominal bloating/distention (FAB), and unspecified FBD (FBD-U). FBD-U is a diagnosis of exclusion and is considered when a patient has bowel symptoms not attributable to an organic etiology and does not meet the criteria for IBS, FC, FDr, or FAB(1,2).
A global prevalence study of over 54,000 individuals across 26 countries found the prevalence of FBD-U to be 8.8% in the general population, a rate significantly higher than all other FBDs except for FC(3). Another recent study of over 1,000 patients who self-identified as IBS and who met Rome IV criteria for any of the 5 functional bowel disorders reported that FBD-U accounted for 11% the sample(4). However, the literature on clinical and psychological characteristics of FBD-U is scarce and it is unclear how these patients' clinical and psychological characteristics differ from other FBDs. In the aforementioned study, Goodoory et al(4) reported that individuals meeting criteria for FBD-U reported abdominal pain at least as often as patients with FC and FDr, reported that symptoms limited their ability to engage fully in daily activities at least as often as FC, FDr, and FAB, and reported having consulted with a physician nearly as often as the other functional bowel disorders. Furthermore, rates of abnormal anxiety, depression, and somatization were comparable or more severe in FBD-U when compared with other functional bowel disorders.
While the diagnosis of FBD-U requires bowel symptoms, there is no clear data on what proportion of these patients have altered bowel habits (constipation, diarrhea, both), abdominal pain, and/or bloating. Moreover, no study to date has investigated why these patients do not meet the criteria for other FBDs. As there are no clinical trials investigating treatment options for FBD-U, understanding why these patients do not meet the criteria for other FBDs would provide us with critical insight into treatment options for FBD-U.
Although the diagnosis of FBD-U requires excluding other FBDs, the Rome IV consensus statement acknowledges that functional bowel disorders (IBS and non-IBS diagnoses) likely exist on a continuum. However, this is based on studies on IBS-C vs. FC(5) and IBS-D vs. FDr(6), which have reported significant gastrointestinal and psychological symptom overlap. Characterizing the overlap and differences between FBD-U and other FBDs would help better understand the heterogeneity of this extremely common FBD. Therefore, the aim of this study was to describe the demographic, gastrointestinal, and psychological symptom profiles of patients with FBD-U presenting to a tertiary care clinic and compare their profiles with other FBDs (such as IBS, FC, and FDr). We also aim to clarify why these patients did not meet the Rome IV criteria for other FBDs.
Materials and Methods
Patients
This was a retrospective study of prospectively collected data. New patients who presented to the IBS & Motility Center at Beth Israel Deaconess Medical Center in Boston, Massachusetts were asked to complete an IRB approved electronic survey prior to their first clinic visit. Their questionnaire data is stored securely on Research Electronic Data Capture (REDCAP), a HIPAA-compliant web-based database. Survey data were extracted from this database for those who completed all ROME IV surveys for lower GI diagnoses between June 2019 and May 2022.
Surveys
Rome IV diagnostic questionnaires
Patients were assessed for the following functional bowel disorders using Rome IV diagnostic surveys(7): IBS, FDr, FC, FAB, and FBD-U. According to Rome IV diagnostic criteria, FBU-U can be diagnosed if patients report bowel symptoms not attributable to an organic etiology that do not meet criteria for IBS, or functional constipation, functional diarrhea or abdominal bloating/distension disorders. These criteria must be fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis. In the current study, to ensure that patients had lower GI symptoms, those responding “not applicable” to questions about predominant bowel habits (constipation/diarrhea/both) were not included in our analyses. This was done in order to ensure that we did not include patients with other DGBIs, such as functional dyspepsia or centrally mediated abdominal pain syndrome, in the diagnosis of FBD-U. Thus, patients who reported altered bowel habits, who did not meet criteria for other organic or functional bowel disorders, and who indicated having at least 1 of the following symptoms -constipation, diarrhea, abdominal pain, or bloating - for at least 6 months, were considered to have FBD-U, figure 1.
Figure 1.
Study inclusion/exclusion criteria for diagnosis of FBD-U
Predominant bowel habit was defined using the Bristol stool form scale (BSFS) based responses to the ROME IV question “In the last three months when you had abnormal stools, what were they usually like”. Patients selected one of the four responses- usually constipated (BSFS 1 or 2), usually diarrhea (BSFS 6 or 7), both constipation and diarrhea (i.e. more than one-fourth of abnormal bowel movements were constipation and more than one-fourth were diarrhea) or not applicable (rarely or never had abnormal bowel habits).
We further identified subgroups of patients with FBDU in order to compare them to other DGBIs. We defined these subgroups as follows: FBD-U with pain included patients who met the above criteria for FBD-U who also reported abdominal pain at least once per week; FBD-U with constipation included individuals with FBD-U who reported constipation as their predominant bowel habit; and FBD-U with diarrhea included FBD-U respondents with diarrhea as their predominant bowel habit. For additional analyses (see supplement), we also identified a subgroup of patients with FBD-U with mixed bowel habits.
Patient Reported Outcomes Measurement Information System (PROMIS) scales
PROMIS questionnaires were developed and validated by the NIH to assess patient-reported symptoms and outcomes. Before their initial visit, patients were administered NIH PROMIS questionnaires for constipation, diarrhea, abdominal pain, anxiety (Short For 7a), and depression (Short Form 8a) in the last week(8-10). PROMIS scores are converted to T-scores, which have a mean of 50 and a standard deviation (SD) of 10 in the US general population.
Healthcare utilization
Patients completed a self-reported questionnaire inquiring about their health care utilization in the 6 months before their initial presentation. This study looked at four separate outcome measures of health care utilization in the past 6 months: (i) PCP visits (yes or no) ii) PCP visits for GI complaints (yes or no) iii) gastroenterology visits (yes or no) and iv) ED visits for GI complaints (yes or no).
Clinical Diagnoses
To compare the ROME IV diagnoses with initial clinical diagnoses made by the gastroenterology providers (board-certified gastroenterologists with expertise in motility disorders), a chart review was performed (initial review performed by SP and NM, reviewed by AE). Initial and follow up visit notes were reviewed to identify clinical diagnosis and to exclude patients who were found to have an organic diagnosis (based on relevant investigations) in 6-12 months after their initial visit.
Statistical Analysis
Statistical analyses were conducted using Statistical Package for the Social Sciences (SPSS). Descriptive statistics included means, standard deviations, and percentages. Categorical data was compared using Chi-square test and continuous data using independent sample T-test/ANOVA as applicable. Post-hoc tests for ANOVA analysis used Bonferroni correction for multiple comparisons. e A P- value <0.05 was considered significant.
Results
During the study period, 1,501 patients completed the initial REDCAP survey and of these 813 met criteria for a ROME IV functional bowel disorder. There were 201 patients who met Rome IV criteria for FBD-U. Seventeen of those patients were diagnosed with an organic disorder and were not included in further analyses. FBD-U was the second most common Rome IV functional bowel diagnosis (13.1%, n=194) after IBS and was more common than FC, FDr and FB (Table 1). Similar to other functional bowel disorders, the majority of FBD-U patients were women (77.2%) although the proportion was lower than that in FB (90.2%), IBS (81.4%), and FC (80.3%). None of the patients meeting criteria for FBD-U were clinically diagnosed with FBD-U (Table 2).
Table 1.
Baseline demographics, symptoms, and healthcare utilization amongst patients with Functional Bowel Disorders (FBDs)
| FBD-U (n=194) |
IBS (n=231) | FC (n=127) |
FDr (n=146) |
FAB (n=41) |
p | |
|---|---|---|---|---|---|---|
| Prevalence of FBD | 13.10% | 15.10% | 9.80% | 9.70% | 2.70% | |
| Age | 51.89 (18.07) | 45.5 (19.55) | 51.16 (21.78) | 48.02 (20.89) | 54.94 (20.23) | 0.003 |
| Sex female | 77.20% | 81.40% | 80.30% | 66.40% | 90.20% | 0.002 |
| % reporting abdominal pain at least 1x/week | 40.30% | 100% | 67% | 61.40% | 41.50% | 0.001 |
| % reporting no abdominal pain | 21.10% | 0% | 10.30% | 13.10% | 19.50% | 0.001 |
| Usual bowel type | 0.001 | |||||
| Diarrhea | 30.90% | 35.70% | 9.60% | 61.40% | 12.80% | |
| Constipation | 36.10% | 22.50% | 67.20% | 2.80% | 28.20% | |
| Both | 33.00% | 38.30% | 18.40% | 35.20% | 25.60% | |
| % reporting bloating at least 1 day per week | 44.70% | 79.60% | 87% | 63.60% | 100% | 0.001 |
| PROMIS pain | 53.49 (12.09) | 64.01 (7.11) | 58.79 (10.43) | 57.13 (11.45) | 51.92 (10.78) | <0.001 |
| PROMIS constipation | 50.44 (7.32) | 56.02 (8.42) | 59.21 (6.35) | NA | 48.07 (7.30) | <0.001 |
| PROMIS diarrhea | 48.61 (9.02) | 56.76 (9.32) | NA | 57.52 (7.49) | 45.65 (7.44) | <0.001 |
| PROMIS anxiety | 53.84 (9.97) | 57.32 (9.02) | 54.22 (10.49) | 54.04 (10.40) | 52.82 (10.60) | <0.001 |
| PROMIS depression | 47.88 (9.11) | 50.83 (9.14) | 48.88 (8.73) | 49.21 (9.36) | 46.48 (9.45) | 0.004 |
| PROMIS sleep | 51.48 (8.11) | 55.35 (8.93) | 52.89 (8.74) | 52.54 (8.33) | 51.03 (8.30) | <0.001 |
| Has seen a PCP in the last 6 months | 79% | 86.20% | 75.00% | 81.00% | 73.70% | 0.075 |
| Has seen a PCP for GI symptoms in the last 6 months | 56.20% | 66.50% | 53.20% | 59.20% | 44.10% | 0.042 |
| Has seen a gastroenterologist in the last 6 months | 41.80% | 46.20% | 43.70% | 45.00% | 25.70% | 0.245 |
| Has seen a specialist other than gastroenterologist in the last 6 months | 56.20% | 56.20% | 58.50% | 52.20% | 55.60% | 0.901 |
PROMIS scores reflect t-scores, Mean (SD); FBD-U – unspecified functional bowel disorder; IBS – irritable bowel syndrome; FC – functional constipation; FDr – functional diarrhea; FAB – functional abdominal bloating
Table 2.
Initial clinical diagnoses for patients later identified as having FBD-U
| Baseline clinical diagnosis | n (%) |
|---|---|
| IBS | 36 (18.6) |
| Functional constipation | 55 (28.4) |
| Functional diarrhea | 15 (7.7) |
| Functional bloating/distention | 14 (7.2) |
| Abdominal pain | 24 (12.4) |
| Upper GI diagnoses | 22 (11.3) |
| Other | 28 (14.4) |
| Total | 194 |
Clinical and psychological characteristics
Weekly abdominal pain
40.3% of FBD-U patients reported at least weekly abdominal pain. By comparison, 67% of FC patients and 61.4% of FDr patients had at least once a week abdominal pain
No abdominal pain
About one-fifth of FBD-U patients (21.1%) did not report any abdominal pain in the last three months (Figure 2), compared to 10.3% and 13.1% of FC and FDr patients.
Figure 2. Percentage of patients with FBD-U who reported abdominal pain at a given frequency over the last 3 months.
FBD-U = Functional Bowel Disorder Unspecified
Predominant bowel habit
In terms of predominant bowel habits in the last three months, 36.1% of FBD-U patients reported constipation, 30.9% reported diarrhea while the remaining 33% reported both diarrhea and constipation. Interestingly, only 44.7% of patients with FBD-U reported at least one day a week bloating, which was much lower than that reported by patients with other functional bowel disorders (63.6% in FDr to 100% in FB) (Table 1).
Symptom severity
ANOVA with post-hoc testing revealed that the severity of abdominal pain was lower in FBD-U patients compared to that reported by patients with IBS, FC, and FDr. FBD-U patients reported less severe constipation compared to IBS and FC patients. They also had less severe diarrhea compared to IBS and FDr patients. These patients also reported lower anxiety, depression, and sleep disturbance scores compared to patients with IBS, but this was comparable to other functional bowel disorders (Table 1, figure 3).
Figure 3. Post-hoc analysis of ANOVA comparing severity of pain, constipation, diarrhea, anxiety, depression and sleep between the 5 functional bowel disorders.
All scores are measured by PROMIS questionnaires (T scores, ranging from 0-100).
ANOVA was significant for each comparison
* p<0.001 on Bonferroni adjusted post-hoc comparison
Healthcare utilization
FBD-U patients reported similar healthcare utilization compared to the patients with other functional bowel disorders. Nearly 42% of patients with FBD-U had seen a gastroenterologist in the last 6 months and 18% had presented to the emergency department for GI symptoms in the last 6 months. This was comparable to patients with IBS, 46% of whom reported seeing a gastroenterologist within the last 6 months and 20% of whom reported having presented to the emergency department for GI symptoms(p>0.05 for both). A larger proportion of IBS patients reported having seen a PCP for GI symptoms in the last 6 months compared to FBD-U (66.5% vs 56.2%, p=0.043) (Table 3).
Table 3.
Comparing healthcare utilization between patients with FBD-U and patients with IBS
| FBDu (n=194) | IBS (n=225) | p-value | |
|---|---|---|---|
| Has seen a PCP in the last 6 months | 79% | 86.20% | 0.058 |
| Has seen a PCP for GI symptoms in the last 6 months | 56.20% | 66.50% | 0.043 |
| Has seen a gastroenterologist in the last 6 months | 41.80% | 46.20% | 0.397 |
| Has seen a specialist other than gastroenterologist in the last 6 months | 56.20% | 56.20% | 0.999 |
| Has been to the ED in the last 6 months for GI reasons | 17.90% | 20.20% | 0.566 |
FBD-U with pain vs. IBS
In order to meet Rome IV criteria for IBS, patients must report at least weekly abdominal pain. We identified a subset of FBD-U patients with at least once a week abdominal pain (n=78) and compared these to patients with IBS (n=231, Table 4). FBD-U patients with at least weekly abdominal pain reported less severe constipation and diarrhea than IBS patients (P<0.001 for each). Similarly, these patients also reported less severe anxiety, depression and sleep disturbance than IBS patients (P<0.05). Abdominal pain severity scores were not statistically different between the FBD-U with pain subgroup and the IBS patients.
Table 4.
Comparing subset of unspecified FBD (FBDU) patients to patients with IBS, FC, and FDr
| Comparing subset of FBDu patients with weekly abdominal pain to IBS patients* | |||
|---|---|---|---|
| FBDU+pain (n=78) |
IBS (n=231) | p-value | |
| Age | 49.02 (17.82) | 45.5 (19.55) | 0.171 |
| Gender (female) | 78.20% | 81.40% | 0.539 |
| Abdominal pain (PROMIS) | 62.48 (8.41) | 64.01 (7.11) | 0.117 |
| Constipation (PROMIS) | 51.64 (8.06) | 56.02 (8.42) | <0.001 |
| Diarrhea (PROMIS) | 49.45 (8.86) | 56.76 (9.32) | <0.001 |
| Anxiety (PROMIS) | 54.30 (10.15) | 57.32 (9.02) | 0.014 |
| Depression (PROMIS) | 48.24 (9.77) | 50.83 (9.14) | 0.034 |
| Sleep (PROMIS) | 52.43 (7.48_ | 55.35 (8.93) | 0.008 |
| Meets IBS criteria for pain associated with defecation | 44.20% | 88.70% | <0.001 |
| Meets IBS criteria for pain associated with change in form of stool | 30.70% | 85.20% | <0.001 |
| Meets IBS criteria for pain associated with change in frequency of stool | 31.10% | 88.60% | <0.001 |
| Meets 3/3 criteria | 20.50% | 73.20% | <0.001 |
| Meets 2/3 criteria | 8.20% | 26.80% | <0.001 |
| Meets 1/3 criteria | 24.70% | NA | NA |
| Meets 0/3 criteria | 46.60% | NA | NA |
| Meets IBS criteria for abdominal pain onset at least 6 months ago | 75.70% | 100% | <0.001 |
| Comparing subset of FBDu patients with usual bowel type constipation with functional constipation (FC) patients** | |||
| FBDU+const (n=70) |
FC (n=127) | p-value | |
| Age | 53.11 (18.87) | 51.16 (21.78) | 0.534 |
| Gender (female) | 77.10% | 80.30% | 0.600 |
| Abdominal pain (PROMIS) | 52.26 (11.54) | 58.79 (10.43) | <0.001 |
| Constipation (PROMIS) | 53.33 (6.98) | 59.21 (6.35) | <0.001 |
| Diarrhea (PROMIS) | NA | NA | |
| Anxiety (PROMIS) | 53.33 (10.20) | 54.22 (10.49) | 0.567 |
| Depression (PROMIS) | 48.02 (9.12) | 48.88 (8.73) | 0.515 |
| Sleep (PROMIS) | 50.48 (8.53) | 52.89 (8.74) | 0.063 |
| Rome FC criteria | |||
| straining >25% of BMs | 44.90% | 87.40% | <0.001 |
| hard/lumpy stools >25% of BMs | 65.70% | 79.40% | 0.036 |
| incomplete evacuation >25% of BMs | 38.80% | 95.20% | <0.001 |
| manual maneuvers >25% of BMs | 11.60% | 28.60% | 0.007 |
| fewer than 3 SBMs per week | 23.90% | 74.20% | <0.001 |
| Loose stools rarely present without laxatives | 73.10% | 100.00% | <0.001 |
| Meets >=2 constipation criteria | 71.40% | 100.00% | <0.001 |
| Meets 1 constipation criteria | 20.60% | NA | |
| Meets 0 | 7.14% | NA | |
| Durationn of constipation >=6 months | 74.20% | 100.00% | <0.001 |
| Comparing subset of FBDu patients with usual bowel type diarrhea with functional diarrhea (FDr) patients*** | |||
| FBDU+dr (n=60) |
FDr (n=146) | p-value | |
| Age | 50.55 (18.94) | 48.02 (20.89) | 0.421 |
| gender (female) | 75.00% | 66.40% | 0.228 |
| Abdominal pain | 54.23 (12.91) | 57.13 (11.45) | 0.116 |
| Constipation (PROMIS) | NA | NA | |
| Diarrhea (PROMIS) | 52.26 (9.08) | 57.53 (7.49) | <0.001 |
| Anxiety (PROMIS) | 54.84 (9.16) | 54.04 (10.39) | 0.603 |
| Depression (PROMIS) | 48.74 (9.15) | 49.21 (9.34) | 0.742 |
| Sleep (PROMIS) | 52.35 (8.20) | 52.54 (8.33) | 0.877 |
| Percent reporting diarrhea >25% of stools in the last 3 months without laxatives | 47.50% | 100.00% | <0.001 |
| Duration of diarrhea >= 6 months | 49.91% | 100.00% | <0.001 |
Standard deviation reported in parentheses
FBDu patients reporting pain at least 1x/week
If Rome usual bowel type is constipation
If Rome usual bowel type is diarrhea
FBDU+pain – FBDU with pain at least once per week
FBDU+const – FBDU with constipation as the predominant bowel habit
FBDU+dr - FBDU with diarrhea as the predominant bowel habit
The Patient-Reported Outcomes Measurement Information System® (PROMIS®) is a validated measure from the National Institute of Health to standardize patient reporting of quality-of-life outcomes.
Applying Rome IV IBS criteria to FBD-U with pain.
Rome IV criteria for IBS requires abdominal pain is associated with at least 2 of the following: 1) defecation; 2) change in stool frequency; and 3) change in stool consistency. About half of FBD-U patients with pain (44.2% of 78) reported that abdominal pain was associated with defecation, 31.1% had abdominal pain associated with a change in stool frequency and 30.7% had abdominal pain associated with a change in stool consistency. About one-fourth of FBD-U patients with pain (28.7%) met at least two of the three above-mentioned criteria (did not meet the criteria for IBS because the onset of abdominal pain was not at least 6 months). Of note, additional one-fourth (24.7%) of these FBD-U patients with pain met one of the three IBS criteria for abdominal pain. Finally, more than three-fourth of the FBD-U patients with pain (75.7%) had the onset of abdominal pain more than 6 months ago.
FBD-U with constipation vs. FC
70 patients with FBD-U (36.1%) reported constipation as their predominant bowel habit. These patients reported less severe abdominal pain and constipation compared to FC patients (P<0.001 for each). However, their psychological profile was very similar to patients with FC (Table 4).
Applying Rome IV FC criteria to FBD-U with constipation.
Rome IV requires that patients meet at least two of the six constipation-related symptoms to qualify for the diagnosis of FC: straining, incomplete evacuation, lumpy or hard stools, infrequent bowel movements, a sensation of anal blockage, and digitalization. 71.4% of patients with FBD-U with constipation as a predominant bowel habit met at least two of the six ROME IV constipation criteria. 74.2% of FBD-U patients with constipation had the onset of constipation symptoms more than 6 months ago and 73.1% reported loose stools were rarely present in absence of laxatives (compared to 100% in the FC group as these are of part of the FC diagnostic criteria).
FBD-U with diarrhea vs. FDr
60 patients with FBD-U (30.9%) reported diarrhea as their predominant bowel habit. FBD-U patients with diarrhea as a predominant bowel habit were similar to FDr patients with respect to all demographic, clinical, and psychological features compared except that they reported less severe diarrhea compared to FDr patients (Table 4). However, of these FBD-U patients with diarrhea as the predominant bowel habit, less than half (47.5%) reported diarrhea >25% of the time in the last three months when they were not taking laxatives while 100% of FDr patients reported diarrhea >25% of the time off laxatives. Also, about half of these FBD-U patients with diarrhea as the predominant bowel habit (49.9%) reported the onset of diarrhea more than 6 months ago.
Supplement table 1 shows FBD-U with constipation, diarrhea, and mixed bowel habits compared to IBS subtypes.
Discussion
A large number of patients in clinical practice meet Rome IV criteria for unspecified functional bowel disorder (FBD-U). Despite this, FBD-U has not been well-studied or well-recognized and there are no evidence-based treatments for this diagnosis. In a sample of 1,500 patients presenting to a tertiary care center, FBD-U was almost as common as IBS and was more common than FC and FDr. Predominant bowel habits in FBD-U were evenly split between constipation, diarrhea, and mixed. Our findings are consistent with a large worldwide prevalence study of 54,000 subjects across 26 nations demonstrating that FBD-U is a very common functional bowel disorder diagnosis(11).
Our study defined FBD-U as patients who reported altered bowel habits (constipation, diarrhea, or both), who did not meet criteria for other bowel disorders, and who reported symptom onset (constipation/diarrhea, abdominal pain, and/or bloating) at least 6 months earlier. The decision to only include patients with altered bowel habits may underrepresent the FBD-U sample, as the Rome IV criteria is not clear as to what constitutes a “bowel symptom”. However, we feel that our definition is appropriate in that it ensures that these patients have lower-GI symptoms and does not include patients with other DGBIs (e.g. centrally mediated abdominal pain syndrome or functional dyspepsia) in the diagnosis of FBD-U. Future iterations of Rome criteria could provide more clarity.
We found that a significant proportion of patients with FBD-U met most of the Rome IV criteria for one of the other functional bowel disorders (IBS, FDr, FC) but did not report the “target” symptom for each diagnosis for at least 6 months (e.g. constipation for FC; diarrhea for FD; abdominal pain for IBS). For example, among the patients with FBD-U with constipation as their predominant bowel habit, almost three-fourths of the patients met the required number of criteria to achieve a Rome IV diagnosis of FC but did not meet full criteria due to not having had constipation for longer than 6 months or having more than rare loose stools without laxative use (instead, they met criteria for FBD-U because the reported abdominal pain or bloating for at least 6 months). Similarly, among the patients with FBD-U with weekly abdominal pain, one-fourth did not meet the required 6-month duration of abdominal pain (instead, they met criteria for FBD-U for having bloating or altered bowel habits for at least 6 months). Therefore, it is likely that the majority of patients who meet criteria for FBD-U fall on the “spectrum” of IBS, FC, or FD symptoms and that these patients may be more accurately characterized as milder or newer manifestations of these conditions. Indeed, Goodooroy et al have reported that only 40% of patients who met criteria for FBD-U at baseline still met criteria at 1 year followup while the remaining 60% met criteria for another functional bowel disorder after 1 year (primarily IBS)(4). A latent class analysis of the same sample suggests that all FBDs might be considered on a spectrum of IBS (12), which is consistent with our hypothesis that FBD-U may represent milder manifestations of other functional bowel disorders.
This significant overlap of FBD-U with other functional bowel disorders is also highlighted by the fact that most of these patients were clinically diagnosed with IBS, FDr, and FC; none of them were clinically diagnosed with FBD-U. Furthermore, patients with FC and FDr, whose diagnoses do not require abdominal pain, often report abdominal pain(6,13,14). Although the diagnosis of FBD-U also does not require abdominal pain, about 80% of patients meeting Rome criteria for FBD-U in our sample reported abdominal pain and 40% reported abdominal pain at least once per week, the threshold required for ROME IV IBS diagnosis. The FBD-U patients also reported utilizing healthcare as often as patients with other functional bowel disorders, despite having less severe abdominal and bowel symptoms, anxiety, depression, and sleep disturbances compared to other functional bowel disorders.
Taken together, these findings would suggest a need for improvement in the Rome IV diagnostic criteria. FBD-U is a diagnosis of exclusion and includes patients with bowel symptoms who do not fulfill the criteria for any of the other functional bowel disorders and do not have an organic cause for their bowel symptoms. Consistent with prior studies(4,12), we have shown that FBD-U exists on a continuum with other functional bowel disorders and has significant clinical and psychosocial overlap. Given the lack of available treatments or planned/ongoing trials to develop treatments for this entity, ideally, the goal should be to minimize the number of patients diagnosed with FBD-U. However, consistent with prior studies(4,11), ours shows that a significant proportion of patients with functional bowel symptoms meet Rome IV diagnosis of FBD-U and therefore are not being represented in mechanistic studies or ongoing/future clinical trials for functional bowel disorders. Thus, future versions of Rome criteria should be less restrictive for other well-defined functional bowel disorders (e.g. IBS), which has been suggested by others too(11,12), to allow more patients to meet criteria for FBDs that have better-outlined treatment algorithms. One potential option is to decrease the required length from symptom onset, which has already been suggested for making a clinical diagnosis of IBS(12,15). In our sample, 25-50% did not meet the FBD criteria due to not having had the target symptom onset (pain for IBS/constipation for FC/diarrhea for FDr) at least 6 months prior. Another consideration for future Rome criteria might be to include other factors, such as bothersomeness of symptoms, which may be more relevant to the treatment of DGBI symptoms.
These findings also raise an important question regarding whether FBD-U should be divided into sub-groups depending on their predominant symptoms. Our data strongly suggests that FBD-U is a heterogeneous diagnosis with varying degrees of abdominal pain, constipation, and/or diarrhea. Based on the results of our chart review, it is clear that patients who meet criteria for FBD-U are often being treated with medications used for other FBDs. Future studies can evaluate whether these medications have similar efficacy in FBD-U as they do in other functional bowel disorders.
Our study has several strengths. First, this study characterizes the clinical and psychosomatic characteristics of patients with FBD-U and compares them with other functional bowel disorders. Also, this study also explores why patients with FBD-U do not meet the criteria for other functional bowel disorders. These patients were evaluated by gastroenterologists with expertise in functional bowel disorders and medical record review was performed to identify any patients who were diagnosed with organic conditions in the months after their initial visit. Thus, the likelihood of missing organic diseases is very low. Our study also has several limitations. First, this study was conducted on a cohort of patients presenting to a tertiary care center. This may hinder generalizability to a larger population in community. Secondly, we recognize that Rome IV questionnaires are not designed for use in clinical practice. Therefore, patients being diagnosed with FBD-U by questionnaire should not impact clinical care, but does impact their eligibility to be represented in clinical trials. Finally, our definition of FBD-U was limited to those who reported altered bowel habits (constipation, diarrhea, or a mix) and did not include patients who reported abdominal pain or bloating without altered bowel habits. As noted above, this may underrepresent the population of those with FBD-U.
In summary, FBD-U is a highly prevalent functional bowel disorder that has not been well studied. Although FBD-U tended to have lower severity of gastrointestinal and psychosocial symptoms, they reported utilizing healthcare resources at a similar rate when compared to the other functional bowel disorders. Given the prevalence of FBD-U in the clinical setting and population levels, a significant proportion of patients with functional bowel disorders are not being represented in mechanistic studies or clinical trials for not having met Rome IV criteria for IBS, FC, or FDr. Therefore, making the ROME IV diagnoses less stringent (e.g. by decreasing the required time since symptom onset) in its future iterations would make it possible to ‘reassign’ these patients to more well-defined entities.
Supplementary Material
Study Highlights.
WHAT IS KNOWN
Unspecified Functional Bowel Disorder is a Rome IV diagnosis of exclusion
FBD-U is common in the general population
WHAT IS NEW HERE
FBD-U was the second most common diagnosis in a tertiary care GI setting
FBD-U tended to have less severe symptoms than other Rome IV FBDs
Patients with FBD-U reported similar rates of healthcare utilization as other FBDs
Financial support:
PS was supported by grant: K23DK129327
Footnotes
Conflict of interest: there is no conflict of interest
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